The TrkB-Shc site signals neuronal survival and local axon growth via MEK and PI3-kinase

To determine how signals emanating from Trk transmit neurotrophin actions i n primary neurons, we tested the ability of TrkB mutated at defined effecto r binding sites to promote sympathetic neuron survival or local axon growth . TrkB stimulated signaling proteins and induced survival and growth in a m anner similar to TrkA. TrkB mutated at the Shc binding site supported survi val and growth poorly relative to wild-type TrkB, whereas TrkB mutated at t he PLC-gamma 1 binding site supported growth and survival well. TrkB-mediat ed neuronal survival was dependent on PI3-kinase and to a lesser extent MEK activity, while growth depended upon both MEK and PI3-kinase activities. T hese results indicate that the TrkB-Shc site mediates both neuronal surviva l and axonal outgrowth by activating the PI3-kinase and MEK signaling pathw ays.